The continued objective of the SCCPRIR program at the University of Illinois will be to conduct innovative basic and clinical research that is of significance to Women's Health. Four interactive projects are proposed to continue to delineate the etiology and pathophysiology of endometriosis in the baboon model and in women as well as address critical questions relating to decidualization and implantation. Project I (Fazleabas) "Endometriosis in the Baboon" will test the hypothesis that endometriotic lesions alter gene expression patterns in eutopic endometrium and that these changes are epigenetic. In studies on CXCL12and glycodelin will provide insight into aberrations in the immune system. Project II (Bulun) "Hormone Action in Endometriosis" will investigate the epigenetic mechanisms for the ERbeta increase in endometriotic stromal cells and determine the transcriptional mechanism is responsible for the decreased ERalpha expression in endometriotic stromal cells. Additional studies will determine the mechanism responsible for down regulation of the PR gene by estradiol in endometriotic stroma. Translational aims will link Projects I and II to test the therapeutic effects of selective steroid hormone receptor modulators. Project III (Nowak) "EMMPRIN Regulates Tissue Remodeling in the Endometrium" will investigate the mechanisms by which EMMPRIN regulates decidualization of endometrial stromal cells and how EMMPRIN promotes the development of endometriosis by increasing angiogenesis and local inflammatory responses in endometriotic lesions. Project IV (Leach) "EGF Family Signaling in Human Implantation" will investigate the underlying mechanism of HB-EGF dependant EGF receptor transactivation in trophoblast necessary for survival and transformation to an invasive phenotype. These projects will be supported by an administrative core and two research cores: A) Imaging and Microscopy and B) Tissue Procurement and Cell Culture. These research cores will operate in an open access formula and support seven other NIH approved grants whose research objectives will contribute but will not infringe upon the goals of the U54 application. The U54 Center at the University of Illinois will continue to be a strong interactive and collegial environment and within an institution that has a rich history in reproductive research.